Relationships of TGFβ1 and TGFβR2 gene polymorphisms with colorectal cancer in Chinese Han population in Shandong area

Objective To study the relationships of TGFβ1 (-509C/T, + 869T/C) and TGFβR2 (-875 G/A) single nucleotide polymorphisms (SNPs) with colorectal cancer (CRC) in Chinese Han population in Shandong. Methods TGFβ1 -509C/T and + 869T/C SNPs in a total of 490 patients with CRC were detected using gene chip. TGFβR2 -875 SNPs was analyzed using PCR-RFLP. TGFβ1 concentrations in serum samples were measured by ELISA. Immunohistochemistry was used to detect the expression of TGFβR2. The relationships of TGFβ1 (-509C/T, + 869T/C) and TGFβR2 (-875 G/A) SNPs with CRC were analyzed through a case-control study. Chi-square test or t test was used for statistical analysis. Relative risk was estimated by odds ratio (OR) and 95% confidence interval (95%CI). Results No significant difference in genotype or allele frequency at TGFβ1 -509/+ 869 was found between patients with CRC and healthy subjects (P>0.05). The frequencies of TGFβR2 -875GG genotype and -875G allele in patients with CRC were significantly higher than those in healthy subjects (-875GG: χ2=4.65, P=0.031, OR=1.32, 95%CI=1.03-1.71; -875G: χ2=4.95, P=0.026, OR=1.29, 95%CI=1.03-1.61). Compare with the healthy control group, higher frequencies of TGFβR2 -875GG genotype and -875G allele were also detected in rectal cancer (-875GG: P=0.04, OR=1.39, 95%CI=1.02-1.95 and -875G: P=0.045, OR=1.32, 95%CI=1.01-1.73), tubular adenocarcinoma (-875GG: P=0.004, OR=1.51, 95%CI=1.14-2.00 and -875G: P=0.003, OR=1.45, 95%CI=1.14-1.85) and highly differentiated tubular adenocarcinoma (-875GG: P=0.003, OR=1.68, 95%CI=1.19-2.38 and -875G: P=0.002, OR=1.62, 95%CI=1.18-2.21) groups. The serum TGFβ1 levels in TGFβR2 -875G carriers with CRC were significantly higher than those in TGFβR2 -875AA carriers in both CRC (t=-3.42, P<0.05) and healthy control (t=-5.09, P<0.001) groups. TGFβR2 expression in -875G carriers with rectal cancer was significantly lower than that in -875AA carriers with rectal cancer (P=0.047) and healthy subjects (P=0.027). Conclusion TGFβR2 -875GG might be a potential risk factor for CRC in Chinese Han population in Shandong and TGFβR2 -875G might be a risk factor for rectal cancer and highly differentiated tubular adenocarcinoma. Key words: Colorectal cancer; TGFβR2; Polymorphism, single nucleotide